Africa aims to avert an mpox pandemic.

Last month, when the world's most populus country, India, reported its first case of the new, highly transmissible clade Ib mpox variant, the challenge of containing the virus was once again evident. Only a few weeks before that in August, the World Health Organization (WHO) and the Africa Centres for Disease Control and Prevention (Africa CDC) declared mpox a public health emergency in response to its spread in Africa. Since then, cases of clade Ib mpox have been reported in Sweden, Thailand, and Pakistan. Although mpox is not yet a global pandemic, the new variant may tip the scales in that direction if the world does not act quickly to mitigate its spread in Africa.

Did smallpox cause stillbirths? Maternal smallpox infection, vaccination, and stillbirths in Sweden, 1780-1839.

While there is strong evidence that maternal smallpox infection can cause foetal loss, it is not clear whether smallpox infections were a demographically important cause of stillbirths historically. In this paper, we use parish-level data from the Swedish Tabellverket data set for 1780-1839 to test the effect of smallpox on stillbirths quantitatively, analysing periods before and after the introduction of vaccination in 1802. We find that smallpox infection was not a major cause of stillbirths before 1820, because most women contracted smallpox as children and were therefore not susceptible during pregnancy. We do find a small, statistically significant effect of smallpox on stillbirths from 1820 to 1839, when waning immunity from vaccination put a greater share of pregnant women at risk of contracting smallpox. However, the reduced prevalence of smallpox in this period limited its impact on stillbirths. Thus, smallpox was not an important driver of historical stillbirth trends.

Mpox global health emergency: Insights into the virus, immune responses, and advancements in vaccines PART II: Insights into the advancements in vaccines.

Mpox is currently a global health emergency. This review (Part II) aims to provide insights into Mpox vaccines and their advancements, offering easily digestible information for healthcare workers and researchers. Current Mpox vaccines are all live-attenuated, previously approved for smallpox, and are classified into non-replicating (Modified Vaccinia Ankara-Bavarian Nordic or MVA-BN) and replicating vaccines (Lister clone16m8 KM Biologic or LC16m8KMB and Acambis2000 or ACAM2000). Replicating vaccines offer long-lasting immunity but are contraindicated for immunocompromised individuals and those with extensive dermatitis. Replicating vaccines are administered as a single dose via epicutaneous scarification, while the non-replicating vaccine is given as two subcutaneous doses. Regulatory approvals in various countries are based on animal challenge studies, with limited effectiveness data available. Only LC16m8 is approved for children in Japan, while the others are approved for individuals aged 18 and older. Clinical trials are currently investigating the efficacy and safety of MVA-BN, particularly in children and for post-exposure prophylaxis (PEP). Novel Mpox vaccines that provide cross-protection against orthopoxviruses are needed, with DNA, subunit, and mRNA platforms under development. MPXV-neutralizing antibody-inducing target antigens for vaccine development include the outer envelope antigens of extracellular enveloped virus (EEV): A35R and B6R, and the inner membrane antigens of intracellular mature virus (IMV): M1R, A29L, H3L, and E8L. Two mRNA vaccines are currently in early clinical stages. Importantly, the COVID-19 pandemic underscored the importance of addressing vaccine disparities and improving global access. Transformative approaches are being explored to overcome this challenge and to enhance access in low- and middle-income countries.

Global prevalence and determinants associated with the acceptance of monkeypox vaccination.

Assessing the acceptance of the monkeypox vaccine is crucial for the success of vaccination programs, yet the prevalence reports remain inconclusive. The aim of this study was to determine the global prevalence of monkeypox vaccine acceptance and identify its associated factors. A meta-analysis was conducted with a comprehensive search strategy on the following databases, including Scopus, Embase, and PubMed, for articles published up to April 5, 2024. This study utilizes a single-arm meta-analysis to calculate the pooled prevalence of monkeypox vaccine acceptance. A Z-test was employed to identify factors associated with the vaccine acceptance. Our study analyzed 51 articles encompassing 98,746 participants, revealing an overall monkeypox vaccine acceptance rate of 65%. Notably, the highest acceptance rates were observed among men who have sex with men (MSMs), while healthcare workers (HCWs) showed the lowest acceptance rates. Additionally, our findings indicated an increased acceptance in individuals with educational attainment beyond a bachelor's degree, a history of COVID-19 and influenza vaccination, homosexual orientation, and HIV-positive status. Conversely, lower acceptance risk was associated with those with educational attainment below a bachelor's degree, heterosexual orientation, and bisexual orientation. In conclusion, our current study has determined the rate of monkeypox vaccine acceptance and identified its associated factors. These findings offer valuable insights as the foundation for targeted policies to manage and increase acceptance rates.

Orthopoxvirus-specific antibodies wane to undetectable levels 1 year after MVA-BN vaccination of at-risk individuals, the Netherlands, 2022 to 2023.

In response to the mpox outbreak in 2022 and 2023, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as JYNNEOS or Imvanex) was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralising antibodies waned to undetectable levels 1 year post vaccination in at-risk individuals who received two doses of MVA-BN administered subcutaneously with an interval of 4 weeks, without prior smallpox or mpox vaccination. Continuous surveillance is essential to understand the impact of declining antibody levels.

Effectiveness of modified vaccinia Ankara-Bavarian Nordic vaccine against mpox infection: emulation of a target trial.

OBJECTIVE: To estimate the real world effectiveness of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine against mpox infection. DESIGN: Emulation of a target trial. SETTING: Linked databases in Ontario, Canada. PARTICIPANTS: 9803 men aged ≥18 years with a history of being tested for syphilis and a laboratory confirmed bacterial sexually transmitted infection (STI) in the previous year, or who filled a prescription for HIV pre-exposure prophylaxis in the previous year. On each day between 12 June 2022 and 27 October 2022, those who had been vaccinated 15 days previously were matched 1:1 with unvaccinated men by age, geographical region, past HIV diagnosis, number of bacterial STI diagnoses in the previous three years, and receipt of any non-MVA-BN vaccine in the previous year. MAIN OUTCOME MEASURE: The main outcome measure was vaccine effectiveness ((1-hazard ratio)×100) of one dose of subcutaneously administered MVA-BN against laboratory confirmed mpox infection. A Cox proportional hazards model was used to estimate hazard ratios to compare the rate of laboratory confirmed mpox between the two groups. RESULTS: 3204 men who received the vaccine were matched to 3204 unvaccinated controls. A total of 71 mpox infections were diagnosed, with 0.09 per 1000 person days (95% confidence interval (CI) 0.05 to 0.13) in the vaccinated group and 0.20 per 1000 person days (0.15 to 0.27) in the unvaccinated group over the study period of 153 days. Estimated vaccine effectiveness of one dose of MVA-BN against mpox infection was 58% (95% CI 31% to 75%). CONCLUSION: The findings of this study, conducted in the context of a targeted vaccination programme and evolving outbreak of mpox, suggest that one dose of MVA-BN is moderately effective in preventing mpox infection.

Discordant performance of mpox serological assays.

BACKGROUND: Since July 23, 2022, global mpox cases reached 92,546, with over 31,000 in the United States. Asymptomatic carriage is a critical mechanism influencing the global dissemination of mpox. Seroprevalence studies are crucial for determining the epidemic's true burden, but uncertainties persist in serologic assay performance and how smallpox vaccination may influence assay interpretation. OBJECTIVES: Our study aimed to assess the performance of several diagnostic assays among mpox-positive, vaccinated, and pre-outbreak negative control samples. This investigation sought to enhance our understanding and management of future mpox outbreaks. STUDY DESIGN: Serum samples from 10 mpox-positive, five vaccinated uninfected, and 137 pre-outbreak controls were obtained for serological testing. The mpox-positive samples were obtained around 100 days post symptom onset, and vaccinated patients were sampled approximately 90 days post-vaccination. Multiple diagnostic assays were employed, including four commercial ELISAs (Abbexa, RayBioTech, FineTest, ProteoGenix) and a multiplex assay (MesoScale Diagnostics (MSD)) measuring five mpox and five smallpox antigens. RESULTS: Three commercial ELISA kits had low specificity (<50 %). The Proteogenix ELISA targeting the E8L antigen had a 94 % sensitivity and 87 % specificity. The E8L antigen on the MSD assay exhibited the greatest distinction between exposure groups, with 98 % sensitivity and 93 % specificity. CONCLUSIONS: None of the assays could distinguish between mpox-positive and vaccinated samples. The MSD assay targeting the MPXV E8L antigen demonstrated the greatest differentiation between mpox-positive and pre-outbreak negative samples. Our findings underscore the imperative to identify sensitive and specific assays to monitor population-level mpox exposure and infection.

The mark of success: The role of vaccine-induced skin scar formation for BCG and smallpox vaccine-associated clinical benefits.

Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health.

The Resurgence of Mpox in Africa.

This Viewpoint discusses the current mpox outbreak in Africa and why countries worldwide must urgently act to address it after the World Health Organization declared the event a Public Health Emergency of International Concern.

As Mpox Cases Surge in Africa, WHO Declares a Global Emergency-Here's What to Know.

This Medical News article discusses the World Health Organization's emergency declaration related to an mpox outbreak in Africa and the emergence of a new virus strain spread by sexual contact.

Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022.

BackgroundIn 2022, a global monkeypox virus (MPXV) clade II epidemic occurred mainly among men who have sex with men. Until early 1980s, European smallpox vaccination programmes were part of worldwide smallpox eradication efforts. Having received smallpox vaccine > 20 years ago may provide some cross-protection against MPXV.AimTo assess the effectiveness of historical smallpox vaccination against laboratory-confirmed mpox in 2022 in Europe.MethodsEuropean countries with sufficient data on case vaccination status and historical smallpox vaccination coverage were included. We selected mpox cases born in these countries during the height of the national smallpox vaccination campaigns (latest 1971), male, with date of onset before 1 August 2022. We estimated vaccine effectiveness (VE) and corresponding 95% CI for each country using logistic regression as per the Farrington screening method. We calculated a pooled estimate using a random effects model.ResultsIn Denmark, France, the Netherlands and Spain, historical smallpox vaccination coverage was high (80-90%) until the end of the 1960s. VE estimates varied widely (40-80%, I2 = 82%), possibly reflecting different booster strategies. The pooled VE estimate was 70% (95% CI: 23-89%).ConclusionOur findings suggest residual cross-protection by historical smallpox vaccination against mpox caused by MPXV clade II in men with high uncertainty and heterogeneity. Individuals at high-risk of exposure should be offered mpox vaccination, following national recommendations, regardless of prior smallpox vaccine history, until further evidence becomes available. There is an urgent need to conduct similar studies in sub-Saharan countries currently affected by the MPXV clade I outbreak.

Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine.

Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage and transport. In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety, and reactogenicity. Non-inferiority of the immune response was assessed by the 95% CI of the geometric mean ratios. Both formulations induced robust vaccinia-specific humoral and cellular immune responses. At peak humoral responses (Week 6), geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At peak cellular responses (Week 2), geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly more local reactions in the FD group. No vaccine-related serious adverse events (SAEs) or vaccine-related AE of special interest were reported. The FD formulation of MVA-BN was shown to be equivalent to MVA-BN LF.

Smallpox Readiness: Modern Strategies Against an Ancient Disease.

This Viewpoint highlights the potential for unintentional or deliberate release of variola virus (smallpox), discusses current medical countermeasures for smallpox, and calls for greater flexibility from the US and its partners in developing safe, reliable, affordable, and equitable countermeasures.

The wet nurses of the Hospital Real of Santiago de Compostela between 1803 and 1808.

Objective: To analyze the duties of wet nurses at the Hospital Real in Santiago de Compostela (Spain). The secondary objectives were to compare the mortality rate and distribution by parish of the foundlings under the care of the Royal House between 1803 and 1808; and to determine the origin of the Galician foundlings who participated in the Royal Philanthropic Expedition of the Smallpox Vaccine in 1803. Methods: Historiographic study that analyzed sorted and not sorted in series indirect positional and quantitative historical sources. Results: The duties of wet nurses during the studied period were to provide basic care and cultural instruction. The mortality rate of foundlings fluctuated during that period and their distribution by parish (functional unit of healthcare services at that time) was similar in those years, with a predominance in the provinces of A Coruña and Pontevedra. A total of 5 Galician foundlings from the House analyzed were part of the smallpox vaccine expedition, their names were Juan Antonio, Jacinto, Gerónimo María, Francisco Florencio and Juan Francisco. Conclusion: During the observed period the wet nurses of the Hospital Real of Santiago de Compostela were in charge of pediatric care. Wet nurses were vital in the role of keeping the foundlings alive and can be considered as one of the forerunners of the pediatric nurse profession at that time.

Global perspectives on smallpox vaccine against monkeypox: a comprehensive meta-analysis and systematic review of effectiveness, protection, safety and cross-immunogenicity.

A large outbreak of monkeypox occurred in 2022, and most people lack immunity to orthopoxvirus. Smallpox vaccination is essential for preventing further smallpox outbreaks. This study evaluated the effectiveness, protection, safety, and cross-immunogenicity of smallpox vaccine in preventing monkeypox infection. PubMed, Embase, Scopus, and Web of Science were searched from database inception to 10 March 2024. We included studies involving "monkeypox virus" and "vaccinations", and excluded reviews, animal studies, and articles with missing or duplicate data. A total of 37 studies with 57,693 participants were included in the final analysis. The effectiveness data showed that monkeypox infection rates were lower in the smallpox-vaccinated group than in the unvaccinated group (risk ratio [RR]: 0.46; 95% confidence interval [CI]: 0.31-0.68). The protection data showed that smallpox vaccination effectively reduced the risk of severe monkeypox infection (RR: 0.61; 95% CI: 0.42-0.87). Third-generation vaccines showed greater efficacy (RR: 0.36, 95% CI: 0.22-0.56) than first-generation vaccines. The number of doses of smallpox vaccine has no significant effect on monkeypox. Safety data showed that adverse reactions after smallpox vaccination were mainly mild and included local erythema, swelling, induration, itching, and pain. Meanwhile, we found that smallpox vaccination could induce the production of neutralizing antibodies against monkeypox. Our findings offer compelling evidence supporting the clinical application of the smallpox vaccine for preventing monkeypox and advocate that high-risk groups should be prioritized for receiving one dose of the smallpox vaccine if the vaccine stockpile is low.

The wet nurses of the Hospital Real of Santiago de Compostela between 1803 and 1808 / Las nodrizas del Hospital Real de Santiago de Compostela entre 1803 y 1808 / As amas de leite do Hospital Real de Santiago de Compostela entre 1803 e 1808

Objective. To analyze the duties of wet nurses at the Hospital Real in Santiago de Compostela (Spain). The secondary objectives were to compare the mortality rate and distribution by parish of the foundlings under the care of the Royal House between 1803 and 1808; and to determine the origin of the Galician foundlings who participated in the Royal Philanthropic Expedition of the Smallpox Vaccine in 1803. Methods. Historiographic study that analyzed sorted and not sorted in series indirect positional and quantitative historical sources.Results. The duties of wet nurses during the studied period were to provide basic care and cultural instruction. The mortality rate of foundlings fluctuated during that period and their distribution by parish (functional unit of healthcare services at that time) was similar in those years, with a predominance in the provinces of A Coruña and Pontevedra. A total of 5 Galician foundlings from the House analyzed were part of the smallpox vaccine expedition, their names were Juan Antonio, Jacinto, Gerónimo María, Francisco Florencio and Juan Francisco. Conclusion. During the observed period the wet nurses of the Hospital Real of Santiago de Compostela were in charge of pediatric care. Wet nurses were vital in the role of keeping the foundlings alive and can be considered as one of the forerunners of the pediatric nurse profession at that time.

Objetivo. analizar las funciones que realizaban las amas de leche en el Hospital Real de Santiago de Compostela (España). Los objetivos secundarios han sido: comparar la mortalidad y distribución por parroquias de los niños expósitos a cargo de la Real Casa entre 1803 y 1808, determinar la procedencia de los niños expósitos gallegos que participaron en la Real Expedición Filantrópica de la Vacuna de la viruela en 1803. Métodos. Estudio historiográfico que analizó fuentes históricas posicionales indirectas y cuantitativas seriadas y no seriadas. Resultados. las funciones de las nodrizas durante el período de estudio eran proporcionar los cuidados básicos e instrucción cultural; la mortalidad de los expósitos sufrió oscilaciones a lo largo del período analizado. La distribución por parroquias (unidad funcional de las áreas de salud en la época) fue similar en estos años, con predominancia de las provincias de A Coruña y Pontevedra. Un total de 5 niños expósitos gallegos de la Casa analizada han participado en la expedición filantrópica de la viruela, sus nombres fueron: Juan Antonio, Jacinto, Gerónimo María, Francisco Florencio y Juan Francisco. Conclusión. Durante el período de observación, las amas de leche del Hospital Real de Santiago de Compostela realizaban cuidados pediátricos. Las nodrizas cumplieron un rol fundamental para el mantenimiento con vida de los niños expósitos y pueden ser consideradas como una de las figuras precursoras de la profesión enfermera pediátrica en la época.

Objetivo. Analisar as funções desempenhadas pelas nutrizes no Hospital Real de Santiago de Compostela (Espanha). Os objetivos secundários foram: comparar a mortalidade e distribuição por freguesia dos enjeitados responsáveis pela Casa Real entre 1803 e 1808, determinar a origem dos enjeitados galegos que participaram na Real Expedição Filantrópica da Vacina contra a Varíola em 1803. Métodos. Estudo historiográfico que analisou fontes históricas posicionais indiretas e quantitativas seriadas e não seriadas. Resultados. As funções das amas de leite durante o período do estudo eram fornecer cuidados básicos e instrução cultural; A mortalidade dos enjeitados oscilou ao longo do período analisado. A distribuição por freguesias (unidade funcional das áreas de saúde da época) foi semelhante nestes anos, com predominância das províncias da Corunha e Pontevedra. Na expedição filantrópica contra a varíola participaram um total de 5 crianças galegas da Casa analisada, os seus nomes eram: Juan Antônio, Jacinto, Gerônimo María, Francisco Florencio e Juan Francisco. Conclusão. Durante o período de observação, as nutrizes do Hospital Real de Santiago de Compostela prestaram cuidados pediátricos. As amas de leite desempenharam um papel fundamental na manutenção da vida dos enjeitados e podem ser consideradas uma das figuras precursoras da profissão de enfermagem pediátrica da época.

Vaccine effectiveness of 3rd generation mpox vaccines against mpox and disease severity: A systematic review and meta-analysis.

INTRODUCTION: Before the global mpox outbreak which began in 2022, the real-world vaccine effectiveness (VE) of mpox vaccines was unknown. We quantified the VE in the global population of 3rd generation or later mpox vaccines (MVA-BN, LC16m8, OrthopoxVac) compared with unvaccinated or other vaccinated states for infection, hospitalization and death. VE was stratified by 1-dose and 2-doses and post-exposure prophylaxis (PEP). METHODS: Studies were included if they measured vaccine efficacy or effectiveness in humans. Animal studies and immunogenicity studies were excluded. MEDLINE, Web of Science, Google Scholar, Embase, MedRxiv and grey literature were searched from January 1st, 1970, with the last search run on November 3, 2023 (Prospero, CRD42022345240). Risk of publication bias was assessed via funnel plots and Egger's test, and study quality via Newcastle-Ottawa scales. RESULTS: A total of 11,892 records were identified via primary search, 3,223 via citation chasing. Thirty-three studies were identified of 3rd generation vaccines, 32 of which were MVA-BN. Two additional studies were re-analysis of existing data. Most of these studies were focused on gay, bisexual, or other men who have sex with men between the ages of 18-49 in May to October of 2022. VE of 1 dose of MVA-BN was 76% (95%CI 64-88%) from twelve studies. VE of 2 doses was 82% (95%CI 72-92%) from six studies. VE of MVA-BN PEP against mpox was 20% (95%CI -24-65%) from seven studies. All VE are calculated from random effects estimates. 18/33(55%) studies were rated as poor, 3/33(9%) as fair and 12/33(36%) as good. Studies included in the meta-analysis had higher quality: 11/16 (69%) were rated as good quality. CONCLUSION: Both 1 and 2 doses of MVA-BN are highly effective at preventing mpox. Effectiveness estimates, specifically of PEP are limited by immortal time bias, predominant mode of mpox transmission, and real-world vaccine timing of administration.

Smallpox vaccination campaigns resulted in age-associated population cross-immunity against monkeypox virus.

Increased human-to-human transmission of monkeypox virus (MPXV) is cause for concern, and antibodies directed against vaccinia virus (VACV) are known to confer cross-protection against Mpox. We used 430 serum samples derived from the Scottish patient population to investigate antibody-mediated cross-neutralization against MPXV. By combining electrochemiluminescence immunoassays with live-virus neutralization assays, we show that people born when smallpox vaccination was routinely offered in the United Kingdom have increased levels of antibodies that cross-neutralize MPXV. Our results suggest that age is a risk factor of Mpox infection, and people born after 1971 are at higher risk of infection upon exposure.